BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.

Objective To investigate the effects of AIDS and tuberculosis(TB)co-infection on CD8+T lymphocytes.Methods Serum CD8+T cells and CD4+T cells were analyzed and compared between human immunodeficiency virus(HIV)alone patients(n=200),TB alone patients(n=200),and HIV/TB co-infection patients(n=200).Results CD8+T cells were significantly higher in HIV alone group compared to HIV/TB co-infection group and TB alone group(x2=128.779,P＜0.001).The level of CD8+T lymphocytes in HIV/TB co-infection group and HIV alone group was higher than normal level(ZHIV/TB=8.343,PHIV/TB＜0.001,ZHIV=7.988,PHIV＜0.001).The CD8+T cells in TB alone group decreased significantly compared with normal levels(ZTB=8.682,PTB＜0.001).The levels of CD4+T cells in the three groups of patients were all lower than normal(ZHIV=11.088,PHIV＜0.001,ZTB=5.562,PTB＜0.001,ZHIV/TB=12.077,PHIV/TB＜0.001).The stratified analysis of CD8+T cell levels by CD4+T cell counts,showed that when CD4+T cell count was≤100 cells/μL,the level of CD8+T cells in HIV alone group was higher than that in TB alone group.HIV alone group had higher CD8+T cells than HIV/TB co-infection group,and the level of CD8+T cells in HIV/TB co-infection group was significantly lower than normal(Z0-100=1.604,P0-100=0.109).When CD4+T cells ≥101 cells/μL,HIV/TB co-infection group had higher CD8+T cells than TB alone group.HIV alone group had higher CD8+T cells than TB alone group.When CD4+T cells＞500 cells/μL,CD8+T cell levels were within the normal range in all three groups of patients.Taking the HIV alone group as a reference,with the decrease of CD4+T cell count,the CD8+T cell count decreased more significantly in TB alone group and HIV/TB co-infection group than in HIV alone group(slope was 0.344 and 0.216,respectively,P＜0.001).Conclusions With the decline of CD4+T cells,both HIV/TB co-infection and TB alone are associated with decrease in CD8+T cells,and the decrease in the TB alone group is more prominent.

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. RESULTS: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. CONCLUSION Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.
Child ; Female ; Humans ; Male ; Azacitidine/therapeutic use* ; Cladribine/therapeutic use* ; Retrospective Studies ; Leukemia, Myeloid, Acute/genetics* ; Neutropenia ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.
Molecular Structure ; Boswellia/chemistry* ; Diterpenes/chemistry* ; Mass Spectrometry

OBJECTIVES: To estimate postmortem interval (PMI) by analyzing the protein changes in skeletal muscle tissues with the protein chip technology combined with multivariate analysis methods. METHODS: Rats were sacrificed for cervical dislocation and placed at 16 ℃. Water-soluble proteins in skeletal muscles were extracted at 10 time points (0 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d and 9 d) after death. Protein expression profile data with relative molecular mass of 14 000-230 000 were obtained. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) were used for data analysis. Fisher discriminant model and back propagation (BP) neural network model were constructed to classify and preliminarily estimate the PMI. In addition, the protein expression profiles data of human skeletal muscles at different time points after death were collected, and the relationship between them and PMI was analyzed by heat map and cluster analysis. RESULTS: The protein peak of rat skeletal muscle changed with PMI. The result of PCA combined with OPLS discriminant analysis showed statistical significance in groups with different time points (P<0.05) except 6 d, 7 d and 8 d after death. By Fisher discriminant analysis, the accuracy of internal cross-validation was 71.4% and the accuracy of external validation was 66.7%. The BP neural network model classification and preliminary estimation results showed the accuracy of internal cross-validation was 98.2%, and the accuracy of external validation was 95.8%. There was a significant difference in protein expression between 4 d and 25 h after death by the cluster analysis of the human skeletal muscle samples. CONCLUSIONS The protein chip technology can quickly, accurately and repeatedly obtain water-soluble protein expression profiles in rats' and human skeletal muscles with the relative molecular mass of 14 000-230 000 at different time points postmortem. The establishment of multiple PMI estimation models based on multivariate analysis can provide a new idea and method for PMI estimation.
Animals ; Humans ; Rats ; Multivariate Analysis ; Postmortem Changes ; Protein Array Analysis ; Technology